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dc.creatorSubotički, Tijana
dc.creatorMitrović-Ajtić, Olivera
dc.creatorBeleslin-Čokić, Bojana
dc.creatorNienhold, Ronny
dc.creatorDiklić, Miloš
dc.creatorĐikić, Dragoslava
dc.creatorLeković, Danijela
dc.creatorBulat, Tanja
dc.creatorMarković, Dragana
dc.creatorGotić, Mirjana
dc.creatorNoguchi, Constance T.
dc.creatorSchechter, Alan N.
dc.creatorSkoda, Radek C.
dc.creatorČokić, Vladan
dc.date.accessioned2021-04-20T12:54:16Z
dc.date.available2021-04-20T12:54:16Z
dc.date.issued2017
dc.identifier.issn0899-1987
dc.identifier.urihttp://rimi.imi.bg.ac.rs/handle/123456789/807
dc.description.abstractIt has been shown that angiogenesis and inflammation play an important role in development of most hematological malignancies including the myeloproliferative neoplasm (MPN). The aim of this study was to investigate and correlate the levels of key angiogenic molecules such as hypoxia-inducible factor-1 (HIF-1), vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) in peripheral blood and bone marrow cells of MPN patients, along with JAK2V617F mutation allele burden and effects of therapy. HIF-1 and VEGF gene expression were decreased, while eNOS mRNA levels were increased in granulocytes of MPN patients. Furthermore, positively correlated and increased VEGF and eNOS protein levels were in negative correlation with HIF-1 levels in granulocytes of MPN patients. According to immunoblotting, the generally augmented angiogenic factors demonstrated JAK2V617F allele burden dependence only in granulocytes of PMF. The angiogenic factors were largely reduced after hydroxyurea therapy in granulocytes of MPN patients. Levels of eNOS protein expression were stimulated by Calreticulin mutations in granulocytes of essential thrombocythemia. Immunocytochemical analyses of CD34(+) cells showed a more pronounced enhancement of angiogenic factors than in granulocytes. Increased gene expression linked to the proinflammatory TGF and MAPK signaling pathways were detected in CD34(+) cells of MPN patients. In conclusion, the angiogenesis is increased in several cell types of MPN patients supported by the transcriptional activation of inflammation-related target genes, and is not limited to bone marrow stroma cells. It also appears that some of the benefit of hydroxyurea therapy of the MPN is mediated by effects on angiogenic factors.en
dc.publisherWiley-Blackwell, Hoboken
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175053/RS//
dc.relationSwiss National Science Foundation (SNSF) European Commission [IZ73Z0_152420]
dc.relationIntramural Research Program at the National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, USA
dc.rightsopenAccess
dc.sourceMolecular Carcinogenesis
dc.subjectangiogenesisen
dc.subjectmyeloproliferative neoplasmen
dc.subjectHIF-1en
dc.subjectVEGFen
dc.subjecteNOSen
dc.titleAngiogenic factors are increased in circulating granulocytes and CD34(+) cells of myeloproliferative neoplasmsen
dc.typearticle
dc.rights.licenseARR
dc.citation.epage579
dc.citation.issue2
dc.citation.other56(2): 567-579
dc.citation.rankM21
dc.citation.spage567
dc.citation.volume56
dc.identifier.doi10.1002/mc.22517
dc.identifier.fulltexthttp://rimi.imi.bg.ac.rs/bitstream/id/620/804.pdf
dc.identifier.pmid27341002
dc.identifier.scopus2-s2.0-84978198792
dc.identifier.wos000392521800022
dc.type.versionpublishedVersion


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